The overall objective of the proposed research is to continue to use the hamster estrogen induced and dependent renal carcinoma as a model to study estrogen carcinogenicity, tumor hormone dependency, and transition of estrogen tumor dependency to autonomy. The significance of steriod receptors in human renal carcinomas will also be assessed. Our aim is to focus our research effort on these 4 areas where information is much needed. First, to elucidate the mechanism of estrogen carcinogenicity and the effect of other steroids and antihormonal agents on this process in the hamster kidney. Our goal is to determine if estrogen carcinogenesis can be affected by known carcinogenic inhibitors; the effect of estrogens on P-448, 450, BP-hydroxylase, epoxide hydrase, glutathione-S-transferase, and peroxidase activities in the hamster kidney and liver; the ability of estrogen intermediates to induce renal tumors in the hamster; to identify metabolites of estrogens derived from hamster kidney and liver microsomal and cell suspension incubations following separation on HPLC and to assess the ability of these metabolites to bind covalently to purified DNA and chromatin; and to seek markers of estrogen action in the untransformed kidney. Second, our demonstration that all major classes of steroid receptors reside in the hamster kidney tumor provide a unique system to study the hormonal interrelationships involved in tumor response to endocrine therapy within a single tissue. Tumor cell suspension and tumor slice preparations will be used to study the effect of various steroids and antihormones, used singly or in combination, on RNA and protein synthesis. Studies will be undertaken to identifiy the chromosomal site (acceptor site) for each steroid receptor complex using partially purified tumor receptors. Third, autonomous tumor variants will be used to determine the nature of the dissociation between progesterone receptor regulation and autonomous tumor growth. Fourth, both cytosol and nuclear steroid receptors in the human renal tumor and effects of steroids on RNA synthesis in human tumor slices studied.